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Melanoma: Immunotherapy for brain metastases 'doubles survival'

Using immunotherapy to treat melanoma that has spread to the brain can significantly improve survival, according to a new analysis of nationwide cancer data in the United States.

Researchers find a new way to boost melanoma survival.

Led by researchers from Brigham and Women's Hospital in Boston, MA, and now published in the journal Cancer Immunology Research, the new study found that "checkpoint blockade immunotherapy" doubled median overall survival in melanoma patients with brain metastases.

Brain metastases are secondary brain tumors that have grown from cancer cells that migrated from a primary tumor elsewhere in the body. They are an advanced stage of cancer that is often challenging to treat.

Until fairly recently, most treatments for melanoma and other types of solid tumor that have spread to the brain have offered "minimal clinical benefit for patients," explains study co-author David Reardon, a professor of medicine at Harvard Medical School in Boston, MA.

But over the past 10 years, there has been a "revolution" in treatments for advanced melanoma that boost the immune system's anticancer powers. Several of these immunotherapies have now been approved.

The new study concerns the use of "immune checkpoint inhibitors," or drugs that block particular proteins in cells. By blocking the targeted proteins, the drugs turbo-charge the immune system's natural ability to target and kill cancer cells.

Melanoma and metastases

Of the cancers that start in the skin, melanoma is the "most dangerous." Although it is among the least common forms of skin cancer, melanoma results in the most deaths.

Official U.S. statistics estimate that there will be "91,270 new cases" of
melanoma in 2018, and 9,320 deaths.

This type of cancer starts when damaged DNA in melanocytes, or the skin cells that make pigment, goes unrepaired. This gives rise to mutated cells that escape elimination by the immune system and go on to replicate and form tumors.

The most common cause of DNA damage in melanocytes is exposure to ultraviolet light, such as from sunlight and tanning beds.

In almost all cases in which melanoma is found early, it can be cured with surgery. But, once the disease reaches an advanced stage and metastasizes to other parts of the body, only around half of patients survive more than 1 year after diagnosis.

Melanoma metastasizes commonly to the brain, but it can also spread to the lungs, liver, and bones. Among metastatic brain cancers, the third most common origin is a melanoma.

More than doubled median survival

Clinical trials of checkpoint blockade immunotherapies in advanced melanoma have shown some promising early results in recent years.

However, the authors note that many of these trials have "excluded or included disproportionately fewer cases" in which melanoma has spread to the brain. The main reason has been about impact on other treatments and whether the drug can actually cross from the bloodstream into the brain.

This had resulted in a lack of information about whether these new immunotherapies might also benefit melanoma patients with brain metastases.

For their investigation, the researchers analyzed data on 2,753 melanoma patients in the National Cancer Database who were diagnosed with "melanoma brain metastases" in hospitals around the U.S. during 2010–2015.

They discovered that the median survival for those who were treated with checkpoint blockade immunotherapies was 12.4 months, which is more than double the 5.2 months median survival for those who did not receive the treatment.

This means that 28.1 percent of the people who received checkpoint blockade immunotherapy were alive 4 years later, compared with just 11.1 percent of those who did not.

The benefit was "even more dramatic" for people whose melanoma had spread only to the brain and not also to other parts of the body, such as the liver or the lungs.

"The results of our analyses indicate that immune checkpoint inhibitors can achieve a meaningful therapeutic benefit for metastatic melanoma, including spread to the central nervous system."

Prof. David Reardon

Meanwhile, there is a need for "much research" to find out why some melanoma patients whose cancer has spread to the central nervous system respond less well to immunotherapy.

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